Approximately one-third of patients with major depressive disorder (MDD) do not respond to existing antidepressants, and those who do generally take weeks to months to achieve a significant effect. There is a clear unmet need for rapidly acting and more efficacious treatments. We will review recent developments in the study of ketamine, an old anaesthetic agent which has shown significant promise as a rapidly acting antidepressant in treatment-resistant patients with unipolar MDD, focusing on clinically important aspects such as dose, route of administration and duration of effect. Additional evidence suggests ketamine may be efficacious in patients with bipolar depression, post-traumatic stress disorder and acute suicidal ideation. We then discuss the safety of ketamine, in which most neuropsychiatric, neurocognitive and cardiovascular disturbances are short lasting; however, the long-term effects of ketamine are still unclear. We finally conclude with important information about ketamine for primary and secondary physicians as evidence continues to emerge for its potential use in clinical settings, underscoring the need for further investigation of its effects.
INTRODUCTIONUnipolar major depressive disorder (MDD) affects approximately 350 million people, making it the leading cause of disability worldwide, associated with harmful consequences onto the well-being of affected individuals and society. 1 2 Currently prescribed antidepressant treatments targeting the monoamine system only alleviate depressive symptoms in about half of the patients.3 These rates become significantly lower in patients who had already failed to improve after two or more antidepressant treatments at adequate doses and duration (ie, treatment-resistant depression, TRD). 4 This results in unnecessary exposure to lengthy trials of ineffective medications. Moreover, currently approved antidepressants targeting the monoamine system have a long onset in initiating response, typically 6-12 weeks. There is a clear unmet need for more efficacious and rapidly acting antidepressants. Emerging evidence of the impaired relationship between the glutamate neurotransmitter system and neuronal plasticity in depression 5 has guided the search for alternative antidepressant treatments. Ketamine is an ionotropic glutamatergic N-methyl-d-aspartate receptor antagonist, on the WHO Essential Medicine List for use as an anaesthetic and prescribed off-label to treat chronic pain.6 7 Research since 2006 on the use of ketamine for treating depression has shown that subanaesthetic doses (0.5 mg/kg) administered over a 40 min intravenous (IV) infusion period can have rapid-acting antidepressant effects on patients with TRD.